Poxviruses

David J Pickup, Duke University Medical Centre, Durham, North Carolina, USA

Published online: April 2010

DOI: 10.1002/9780470015902.a0001083.pub2

Poxviruses are brick-shaped, enveloped viruses, each containing a linear, double-stranded DNA (deoxyribonucleic acid) genome of 130–380 kilobases (kb). Several family members, including variola, monkeypox, cowpox, vaccinia, orf and molluscum contagiosum viruses, cause disease in humans. Smallpox, which was caused by variola virus, was once responsible for the deaths of millions each year. In 1796, Jenner showed that inoculation of material from a cowpox lesion could protect against smallpox: Vaccination had been introduced into medicine. Moreover, through the use of cowpox and vaccinia virus vaccines, the dread disease of smallpox was eradicated from the natural environment. Although variola virus, the principal poxvirus pathogen, is no longer a public health hazard, the poxviruses have continued to be the focus of intense study because they provide unique systems for investigation of mechanisms important in molecular biology, viral pathogenicity and immunity. Attenuated poxviruses now provide some of the most promising contemporary platforms for broad-spectrum, live-virus vaccines.

Key concepts

  • Variola virus, which causes smallpox, is one of the most virulent human pathogens.
  • Variola virus is the only virus eradicated from the natural environment.
  • Jenner showed that infection with cowpox could protect against infection with smallpox.
  • Cowpox virus was the original vaccine, hence the name vaccine, from the Latin word vacca for cow.
  • The worldwide eradication of the disease of smallpox was achieved by immunization with vaccines containing live vaccinia viruses (viruses similar to, but more attenuated than, cowpox virus).
  • Except for variola virus and molluscum contagiosum virus (MCV), most of the poxvirus diseases of humans are zoonoses (diseases transmitted to humans from animals).
  • Among viruses, the poxviruses are unusually independent of host cell functions, employing mainly viral enzymes for viral gene transcription and viral DNA replication in the cytoplasm of infected cells.
  • Poxviruses do not establish latent infections.
  • Poxviruses possess many accessory genes that are not required for virus replication in vitro, but which are advantageous for virus replication in vivo.
  • Most of the accessory proteins encoded by poxviruses of vertebrates interfere with either innate or adaptive immune responses.

Keywords: cowpox; vaccinia; smallpox; vaccines; viral replication; virus–host interactions

Figure 1. The poxvirus replication cycle. The Cowpox virus replication cycle is depicted diagrammatically progressing from left to right. The upper panel shows morphological features of replication: (1) attachment, fusion and entry of the virus particles, where the EV outer membrane is disrupted, or the matrix of the ATI is solubilized to release an MV capable of attachment to and fusion with the plasma membrane; (2) the uncoating of the MV to generate the cores; (3) the formation of viroplasm in the viral factories, or viral B-type inclusions; (4) the morphogenetic pathway leading from crescents to the formation of immature virus particles (IVs) which may contain electron-dense condensed regions; (5) transition of the IVs into the mature virions (MVs); (6) the MVs subsequently enter one of the three pathways, namely retention in the cytoplasm, or conversion into MVs embedded within the A-type inclusions (ATIs), or conversion into the wrapped virions (WVs) possessing two additional membrane layers. The WVs are transported to the plasma membrane on microtubules. At the cell periphery, the outermost membrane of the WV fuses with the plasma membrane to produce an EV on the outer surface of the cell. This particle is then propelled from the cell on the tips of microvilli generated by the formation of actin tails in the cytoplasm under the cell-associated EV. The EVs are projected from live cells. The residual MVs in the cytoplasm and the ATIs containing embedded MVs are released on the death and disintegration of the infected cell. The lower panel depicts the onset of the various stages of the replication cycle relative to the time of infection.
Figure 2. Intermediates in poxvirus morphogenesis. A transmission electron micrograph of a thin section through the cytoplasm of a cell infected with Vaccinia virus showing several intermediate forms of the virus particle. Key: C, crescent; IV, immature virion; MV, mature virion and V, viroplasm (granular material containing viral DNA and proteins). The arrows indicate progressively more mature forms of virus particle. Note the characteristic dumbbell-shaped core in the MV at the right-hand edge of the figure. Electron micrograph courtesy of Dr Sara E Miller (Department of Pathology, Duke University Medical Centre).
close
 References
    Afonso CL, Tulman ER, Lu Z et al. (1999) The genome of Melanoplus sanguinipes entomopoxvirus. Journal of Virology 73: 533–552.
    Alzhanova D, Edwards DM, Hammarlund E et al. (2009) Cowpox virus inhibits the transporter associated with antigen processing to evade T cell recognition. Cell Host & Microbe 6: 433–445.
    Bergman N, Moraes KC, Anderson JR et al. (2007) Lsm proteins bind and stabilize RNAs containing 5¢ poly(A) tracts. Nature Structural Molecular Biology 14: 824–831.
    Berhanu A, King DS, Mosier S et al. (2009) ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation. Antimicrobial Agents and Chemotherapy 53: 4999–5009.
    van Buuren N, Couturier B, Xiong Y and Barry M (2008) Ectromelia virus encodes a novel family of F-box proteins that interact with the SCF complex. Journal of Virology 82: 9917–9927.
    Byun M, Verweij MC, Pickup DJ et al. (2009) Two mechanistically distinct immune evasion proteins of cowpox virus combine to avoid antiviral CD8T cells. Cell Host & Microbe 6: 422–432.
    Campbell JA, Trossman DS, Yokoyama WM and Carayannopoulos LN (2007) Zoonotic orthopoxviruses encode a high-affinity antagonist of NKG2D. Journal of Experimental Medicine 204: 1311–1317.
    Comeau MR, Johnson R, DuBose RF et al. (1998) A poxvirus-encoded semaphorin induces cytokine production from monocytes and binds to a novel cellular semaphorin receptor, VESPR. Immunity 8: 473–482.
    Cudmore S, Cossart P, Griffiths G and Way M (1995) Actin-based motility of vaccinia virus. Nature 378: 636–638.
    Damon I, Murphy PM and Moss B (1998) Broad spectrum chemokine antagonistic activity of a human poxvirus chemokine homolog. Proceedings of the National Academy of Sciences of the USA 95: 6403–6407.
    De Silva FS, Lewis W, Berglund P, Koonin EV and Moss B (2007) Poxvirus DNA primase. Proceedings of the National Academy of Sciences of the USA 104: 18724–18729.
    book Fenner F, Henderson DA, Arita I, Jezek Z and Ladnyi ID (1988a) "The clinical features of smallpox". In: Smallpox and Its Eradication, pp. 1–68. Geneva: World Health Organization.
    book Fenner F, Henderson DA, Arita I, Jezek Z and Ladnyi ID (1988b) "The intensified smallpox eradication programme, 1967–1980". In: Smallpox and Its Eradication. Geneva: World Health Organization.
    Fleming SB, McCaughan CA, Andrews AE, Nash AD and Mercer AA (1997) A homolog of interleukin-10 is encoded by the poxvirus orf virus. Journal of Virology 71: 4857–4861.
    Garcia AD and Moss B (2001) Repression of vaccinia virus Holliday junction resolvase inhibits processing of viral DNA into unit-length genomes. Journal of Virology 75: 6460–6471.
    Gubser C, Hue S, Kellam P and Smith GL (2004) Poxvirus genomes: a phylogenetic analysis. Journal of General Virology 85: 105–117.
    Hammarlund E, Dasgupta A, Pinilla C et al. (2008) Monkeypox virus evades antiviral CD4+ and CD8+ T cell responses by suppressing cognate T cell activation. Proceedings of the National Academy of Sciences of the USA 105: 14567–14572.
    Johnston JB, Barrett JW, Nazarian SH et al. (2005) A poxvirus-encoded pyrin domain protein interacts with ASC-1 to inhibit host inflammatory and apoptotic responses to infection. Immunity 23: 587–598.
    Kotwal GJ, Isaacs SN, McKenzie R, Frank MM and Moss B (1990) Inhibition of the complement cascade by the major secretory protein of vaccinia virus. Science 250: 827–830.
    Langland JO, Kash JC, Carter V et al. (2006) Suppression of proinflammatory signal transduction and gene expression by the dual nucleic acid binding domains of the vaccinia virus E3L proteins. Journal of Virology 80: 10083–10095.
    Law M, Carter GC, Roberts KL, Hollinshead M and Smith GL (2006) Ligand-induced and nonfusogenic dissolution of a viral membrane. Proceedings of the National Academy of Sciences of the USA 103: 5989–5994.
    Law M, Hollinshead M, Lee HJ and Smith GL (2004) Yaba-like disease virus protein Y144R, a member of the complement control protein family, is present on enveloped virions that are associated with virus-induced actin tails. Journal of General Virology 85: 1279–1290.
    Li P, Wang N, Zhou D et al. (2005) Disruption of MHC class II-restricted antigen presentation by vaccinia virus. Journal of Immunology 175: 6481–6488.
    Lyttle DJ, Fraser KM, Fleming SB, Mercer AA and Robinson AJ (1994) Homologs of vascular endothelial growth factor are encoded by the poxvirus orf virus. Journal of Virology 68: 84–92.
    Mohamed MR and McFadden G (2009) NFB inhibitors: strategies from poxviruses. Cell Cycle 8: 3125–3132.
    Moss B (1996) Genetically engineered poxviruses for recombinant gene expression, vaccination, and safety. Proceedings of the National Academy of Sciences of the USA 93: 11341–11348.
    Moss B (2006) Poxvirus entry and membrane fusion. Virology 344: 48–54.
    book Moss B (2007) "Poxviridae: the viruses and their replication". In: Knipe DM and Howley PM (eds) Fields’ Virology, pp. 2905–2945. Philadelphia, PA: Lippincott Williams and Wilkins.
    Paoletti E (1996) Applications of pox virus vectors to vaccination: an update. Proceedings of the National Academy of Sciences of the USA 93: 11349–11353.
    Perdiguero B and Esteban M (2009) The interferon system and vaccinia virus evasion mechanisms. Journal of Interferon and Cytokine Research 29: 581–598.
    Ray CA, Black RA, Kronheim SR et al. (1992) Viral inhibition of inflammation: cowpox virus encodes an inhibitor of the interleukin-1 beta converting enzyme. Cell 69: 597–604.
    Roberts KL and Smith GL (2008) Vaccinia virus morphogenesis and dissemination. Trends in Microbiology 16: 472–479.
    Sale TA, Melski JW and Stratman EJ (2006) Monkeypox: an epidemiologic and clinical comparison of African and US disease. Journal of the American Academy of Dermatology 55: 478–481.
    Sanderson CM, Hollinshead M and Smith GL (2000) The vaccinia virus A27L protein is needed for the microtubule-dependent transport of intracellular mature virus particles. Journal of General Virology 81: 47–58.
    Satheshkumar PS and Moss B (2009) Characterization of a newly identified 35-amino-acid component of the vaccinia virus entry/fusion complex conserved in all chordopoxviruses. Journal of Virology 83: 12822–12832.
    Seet BT, Johnston JB, Brunetti CR et al. (2003) Poxviruses and immune evasion. Annual Review of Immunology 21: 377–423.
    Senkevich TG, Koonin EV and Moss B (2009) Predicted poxvirus FEN1-like nuclease required for homologous recombination, double-strand break repair and full-size genome formation. Proceedings of the National Academy of Sciences of the USA 106: 17921–17926.
    Shirokikh NE and Spirin AS (2008) Poly(A) leader of eukaryotic mRNA bypasses the dependence of translation on initiation factors. Proceedings of the National Academy of Sciences of the USA 105: 10738–10743.
    Smee DF (2008) Progress in the discovery of compounds inhibiting orthopoxviruses in animal models. Antiviral Chemistry & Chemotherapy 19: 115–124.
    Sonnberg S, Seet BT, Pawson T, Fleming SB and Mercer AA (2008) Poxvirus ankyrin repeat proteins are a unique class of F-box proteins that associate with cellular SCF1 ubiquitin ligase complexes. Proceedings of the National Academy of Sciences of the USA 105: 10955–10960.
    Stroobant P, Rice AP, Gullick WJ et al. (1985) Purification and characterization of vaccinia virus growth factor. Cell 42: 383–393.
    Taylor JM and Barry M (2006) Near death experiences: poxvirus regulation of apoptotic death. Virology 344: 139–150.
    Tewalt EF, Grant JM, Granger EL et al. (2009) Viral sequestration of antigen subverts cross presentation to CD8(+) T cells. PLoS Pathogens 5: e1000457.
    Twardzik DR, Brown JP, Ranchalis JE, Todaro GJ and Moss B (1985) Vaccinia virus-infected cells release a novel polypeptide functionally related to transforming and epidermal growth factors. Proceedings of the National Academy of Sciences of the USA 82: 5300–5304.
    Upton C, Slack S, Hunter AL, Ehlers A and Roper RL (2003) Poxvirus orthologous clusters: toward defining the minimum essential poxvirus genome. Journal of Virology 77: 7590–7600.
    Vanderplasschen A, Mathew E, Hollinshead M, Sim RB and Smith GL (1998) Extracellular enveloped vaccinia virus is resistant to complement because of incorporation of host complement control proteins into its envelope. Proceedings of the National Academy of Sciences of the USA 95: 7544–7549.
    Wagenaar TR and Moss B (2007) Association of vaccinia virus fusion regulatory proteins with the multicomponent entry/fusion complex. Journal of Virology 81: 6286–6293.
    Walzer T, Galibert L and De Smedt T (2005) Poxvirus semaphorin A39R inhibits phagocytosis by dendritic cells and neutrophils. European Journal of Immunology 35: 391–398.
    Wang N, Weber E and Blum JS (2009) Diminished intracellular invariant chain expression after vaccinia virus infection. Journal of Immunology 183: 1542–1550.
    Wiebe MS and Traktman P (2007) Poxviral B1 kinase overcomes barrier to autointegration factor, a host defense against virus replication. Cell Host & Microbe 1: 187–197.
 Further Reading
    Arif BM (1995) Recent advances in the molecular biology of entomopoxviruses. Journal of General Virology 76(part 1): 1–13.
    Broyles SS (2003) Vaccinia virus transcription. Journal of General Virology 84: 2293–2303.
    Drexler I, Staib C and Sutter G (2004) Modified vaccinia virus Ankara as antigen delivery system: how can we best use its potential? Current Opinion in Biotechnology 15: 506–512.
    Du S and Traktman P (1996) Vaccinia virus DNA replication: two hundred base pairs of telomeric sequence confer optimal replication efficiency on minichromosome templates. Proceedings of the National Academy of Sciences of the USA 93: 9693–9698.
    Essbauer S, Pfeffer M and Meyer H (2010) Zoonotic poxviruses. Veterinary Microbiology 140: 229–236.
    Fenner F (2000) Adventures with poxviruses of vertebrates. FEMS Microbiology Reviews 24: 123–133.
    Hornung V, Ablasser A, Charrel-Dennis M et al. (2009) AIM2 recognizes cytosolic dsDNA and forms a caspase-1-activating inflammasome with ASC. Nature 458: 514–518.
    Jacobs BL, Langland JO, Kibler KV et al. (2009) Vaccinia virus vaccines: past, present and future. Antiviral Research 84: 1–13.
    Smith GL, Murphy BJ and Law M (2003) Vaccinia virus motility. Annual Review of Microbiology 57: 323–342.

Related Sub-Topics:

DNA Viruses | Viruses Infecting Humans | Viruses Infecting Animals
Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Poxviruses
 
How to Cite close
Pickup, David J(Apr 2010) Poxviruses. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0001083.pub2]